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The Novel WT1 Gene Mutation p.H377N Associated to Denys-Drash Syndrome

Guaragna, Mara Sanches BSc*; Soardi, Fernanda Caroline PhD*; Assumpção, Juliana Godoy PhD; Zambaldi, Lílian de Jesus Girotto BSc; Cardinalli, Izilda Aparecida MD, PhD; Yunes, José Andrés PhD; de Mello, Maricilda Palandi PhD*; Brandalise, Silvia Regina MD, PhD† ‡; Aguiar, Simone dos Santos MD, PhD

Journal of Pediatric Hematology/Oncology: August 2010 - Volume 32 - Issue 6 - pp 486-488
doi: 10.1097/MPH.0b013e3181e5e20d
Clinical and Laboratory Observations

Denys-Drash syndrome (DDS, Online Mendelian Inheritance in Man number 194080) is a rare human developmental disease generally occurring in 46,XY individuals characterized by the combination of disorder of sex development, early onset nephropathy, and Wilms' tumor (WT). DDS is mainly caused by mutations in the WT1 gene. This report describes a novel WT1 gene mutation in a DDS patient. Sequencing the WT1 gene revealed a heterozygous transversion CAT>AAT within exon 8, causing the substitution of an asparagine for a histidine at residue 377. The p.H377N mutation is predicted to diminish the WT1 protein DNA-binding affinity as it might disrupt the normal zinc finger 2 conformation.

*Laboratório de Genética Molecular Humana, Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas

Laboratório de Biologia Molecular, Centro Infantil Boldrini

Departamento de Pediatria, Universidade Estadual de Campinas, Campinas, Sao Paulo, Brasil

Supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Reprints: Simone dos Santos Aguiar, MD, PhD, Centro Infantil Boldrini, Rua Dr Gabriel Porto 1270, 13083-210 Campinas, Sao Paulo, Brazil (e-mail: simone@boldrini.org.br).

Received for publication December 3, 2009; accepted April 20, 2010

© 2010 Lippincott Williams & Wilkins, Inc.